Action observation as a tool for neurorehabilitation to moderate motor deficits and aphasia following stroke

The mirror neuron system consists of a set of brain areas capable of matching action observation with action execution. One core feature of the mirror neuron system is the activation of motor areas by action observation alone. This unique capacity of the mirror neuron system to match action perception and action execution stimulated the idea that mirror neuron system plays a crucial role in the understanding of the content of observed actions and may participate in procedural learning. These features bear a high potential for neurorehabilitation of motor deficits and of aphasia following stroke. Since the first articles exploring this principle were published, a growing number of follow-up studies have been conducted in the last decade. Though, the combination of action observation with practice of the observed actions seems to constitute the most powerful approach. In the present review, we present the existing studies analyzing the effects of this neurorehabJlitative approach in clinical settings especially in the rehabilitation of stroke associated motor deficits and give a perspective on the ongoing trials by our research group. The data obtained up to date showed significant positive effect of action observation on recovery of motor functions of the upper limbs even in the chronic state after stroke, indicating that our approach might become a new standardized add-on feature of modern neurorehabilitative treatment schemes.

The use of mirror mechanism for activity-dependent neurorehabilitation

The present study observed the effects of the non-invasive, mirror neuron system application on neurorehabilitation. In primate studies, mirror neurons have been shown to fire when the subject observes or performs a specific action, thereby allowing for observation of motor cortex activation. This activation of the mirror neuron system could serve as a treatment for stroke patients. In the present study, the combination of a mirror neuron system-based therapy was introduced for the treatment of patients with motor-deficits, who could not perform rehabilitation exercises. The results also indicate that this therapeutic method plays a positive role in emotional regulation in the same patients.

Virtual Reality Neurorehabilitation

The present work investigates the application of virtual reality(VR)technology to neurorehabilitation.By consulting a wealth of data,the advantages of VR in neurorehabilitation are introduced,followed by the application status of VR in the rehabilitation of stroke patients,Parkinson’s patients,mental and psychological diseases.Besides,many research experiments on the application of VR technology in rehabilitation medicine at the present stage are investigated.The results indicate that compared with traditional balance training,the VR-based neurological rehabilitation training method can more effectively ease the tilt degree and strengthen the trunk control ability and balance function of patients with post-stroke tilt syndrome.When the effect of traditional rehabilitation training on the gait and balance of Parkinson’s patients is not good enough,VR-based rehabilitation training can at least be used as an alternative therapy.Moreover,VR games have made great breakthroughs in promoting limb rehabilitation and brain injury rehabilitation,which is of incredible benefit to those with motor and activity disorders.It is also beneficial to the treatment and recovery of mental disorders of patients with nerve injury.Although VR still has limitations such as high cost and technical breakthrough bottleneck,it has great advantages in relieving pain,enhancing interest,and recovering patients’mental health in neurological rehabilitation training.

An ultrasound-guided percutaneous electrical nerve stimulation regimen devised using finite element modeling promotes functional recovery after median nerve transection

Percutaneous electrical nerve stimulation of an injured nerve can promote and accelerate peripheral nerve regeneration and improve function.When performing acupuncture and moxibustion,locating the injured nerve using ultrasound before percutaneous nerve stimulation can help prevent further injury to an already injured nerve.However,stimulation parameters have not been standardized.In this study,we constructed a multi-layer human forearm model using finite element modeling.Taking current density and activated function as optimization indicators,the optimal percutaneous nerve stimulation parameters were established.The optimal parameters were parallel placement located 3 cm apart with the injury site at the midpoint between the needles.To validate the efficacy of this regimen,we performed a randomized controlled trial in 23 patients with median nerve transection who underwent neurorrhaphy.Patients who received conventional rehabilitation combined with percutaneous electrical nerve stimulation experienced greater improvement in sensory function,motor function,and grip strength than those who received conventional rehabilitation combined with transcutaneous electrical nerve stimulation.These findings suggest that the percutaneous electrical nerve stimulation regimen established in this study can improve global median nerve function in patients with median nerve transection.

Working-memory training improves developmental dyslexia in Chinese children

Although plasticity in the neural system underlies working memory, and working memory can be improved by training, there is thus far no evidence that children with developmental dyslexia can benefit from working-memory training. In the present study, thirty dyslexic children aged 8-11 years were recruited from an elementary school in Wuhan, China. They received working-memory training including training in visuospatial memory, verbal memory, and central executive tasks. The difficulty of the tasks was adjusted based on the performance of each subject, and the training sessions lasted 40 minutes per day, for 5 weeks. The results showed that working-memory training significantly enhanced performance on the nontrained working memory tasks such as the visuospatial, the verbal domains, and central executive tasks in children with developmental dyslexia. More importantly, the visual rhyming task and reading fluency task were also significantly improved by training. Progress on working memory measures was related to changes in reading skills. These experimental findings indicate that working memory is a pivotal factor in reading development among children with developmental dyslexia, and interventions to improve working memory may help dyslexic children to become more proficient in reading.

Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury

A large body of evidence shows that spinal circuits are significantly affected by training, and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection. However, after incomplete lesions, the effect of treadmil training has been debated, which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects. In this study, rats with moderate spinal cord contusion were sub-jected to either step training on a treadmil or used in the model （control） group. The treadmil training began at day 7 post-injury and lasted 20 ± 10 minutes per day, 5 days per week for 10 weeks. The speed of the treadmil was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat. After 3 weeks of step training, the step training group exhibited a sig-nificantly greater improvement in the Basso, Beattie and Bresnahan score than the model group. The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury, while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups. These results suggest that treadmil training significantly improves functional re-covery and neural plasticity after incomplete spinal cord injury.

Transcranial magnetic stimulation in animal models of neurodegeneration

Brain stimulation techniques offer powerful means of modulating the physiology of specific neural structures. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation(TMS) and transcranial direct current stimulation, have emerged as therapeutic tools for neurology and neuroscience. However, the possible repercussions of these techniques remain unclear, and there are few reports on the incisive recovery mechanisms through brain stimulation. Although several studies have recommended the use of non-invasive brain stimulation in clinical neuroscience, with a special emphasis on TMS, the suggested mechanisms of action have not been confirmed directly at the neural level. Insights into the neural mechanisms of non-invasive brain stimulation would unveil the strategies necessary to enhance the safety and efficacy of this progressive approach. Therefore, animal studies investigating the mechanisms of TMSinduced recovery at the neural level are crucial for the elaboration of non-invasive brain stimulation. Translational research done using animal models has several advantages and is able to investigate knowledge gaps by directly targeting neuronal levels. In this review, we have discussed the role of TMS in different animal models, the impact of animal studies on various disease states, and the findings regarding brain function of animal models after TMS in pharmacology research.

Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise （15-22 m/min, 25-64 minutes） and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus （P = 0.04） and plasma level of total antioxidant capacity of rats exposed to lead acetate （P 〈 0.001）, and significantly decreased plasma level of malondialdehyde （P 〈 0.001）. Acute exercise only decreased the hippocampal malondialdehyde level （P = 0.09） and increased brain-derived neurotrophic factor level in the hippocampus （P = 0.66）. Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly （P = 0.99）, These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

Recovery from prolonged disorders of consciousness:A dual-center prospective cohort study in China

BACKGROUND Recent innovations in intensive care have improved the prognosis of patients with severe brain injuries and brought more patients with disorders of consciousness(DoC).Data are lacking regarding the long-term outcomes of those patients in China.It is necessary to study the long-term outcomes of patients with prolonged DoC in light of many factors likely to influence crucial decisions about their care and their life.AIM To present the preliminary results of a DoC cohort.METHODS This was a two-center prospective cohort study of inpatients with vegetative state(VS)/unresponsive wakefulness syndrome(UWS).The study outcomes were the recovery from VS/UWS to minimally conscious state(MCS)and the long-term status of patients with prolonged DoC considered in VS/UWS or MCS for up to 6 years.The patients were evaluated using the Glasgow coma scale,coma recovery scale-revised,and Glasgow outcome scale.The endpoint of follow-up was recovery of full consciousness or death.The changes in the primary clinical outcome improvement in clinical diagnosis were evaluated at 12 mo compared with baseline.RESULTS The study population included 93 patients(62 VS/UWS and 31 MCS).The postinjury interval range was 28-634 d.Median follow-up was 20 mo(interquartile range,12-37 mo).At the endpoint,33 transitioned to an emergence from MCS or full consciousness,eight had a locked-in syndrome,and there were 35 patients remaining in a VS/UWS and 11 in an MCS.Seven(including one locked-in syndrome)patients(7.5%)died within 12 mo of injury.Compared with the unresponsive group(n=52)at 12 mo,the responsive group(n=41)had a higher proportion of males(87.8%vs 63.5%,P=0.008),shorter time from injury(median,40.0 d vs 65.5 d,P=0.006),higher frequency of vascular etiology(68.3%vs 38.5%,P=0.007),higher Glasgow coma scale score at admission(median,9 vs 6,P<0.001),higher coma recovery scale-revised score at admission(median,9 vs 2.5,P<0.001),at 1 mo(median,14 vs 5,P<0.001),and at 3 mo(median,20 vs 6,P<0.001),lower frequency of VS/UWS(36.6%vs 90.0%,P<0.001),and more favorable Glasgow outcome scale outcome(P<0.001).CONCLUSION Patients with severe DoC,despite having strong predictors of poor prognosis,might recover consciousness after a prolonged time of rehabilitation.An accurate initial diagnosis of patients with DoC is critical for predicting outcome and a long-term regular follow-up is also important.

Is transcranial direct current stimulation a potential method for improving response inhibition?

Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area （pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase）. Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

Therapeutic benefit of repetitive transcranial magnetic stimulation for severe mirror movements A case report

Congenital mirror movements retard typical hand functions, but no definite therapeutic modality is available to treat such movements. We report an 8-year-old boy with severe mirror movements of both hands. His mirror movements were assessed using the Woods and Teuber grading scale and his fine motor skills were also evaluated by the Purdue Pegboard Test. A 2-week regimen of repetitive transcranial magnetic stimulation produced markedly diminished mirror movement symptoms and increased the fine motor skills of both hands. Two weeks after the completion of the regimen, mirror movement grades had improved from grade 4 to 1 in both hands and the Purdue Pegboard Test results of the right and left hands also improved from 12 to 14 or 13. These improvements were maintained for 1 month after the 2-week repetitive transcranial magnetic stimulation regimen. After 18 months, the mirror movement grade was maintained and the Purdue Pegboard test score had improved to 15 for the right hand while the left hand score was maintained at 13. This occurred without any additional repetitive transcranial magnetic stimulation or other treatment. These findings suggest that repetitive transcranial magnetic stimulation for this patient had a therapeutic and long-term effect on mirror movements.

Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain

The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise ＋ light groups （n = 9 per group）. The rats in the exercise group were subjected to treadmill exercise （5 days per week, 30 minutes per day, over a 4-week period）, the light group rats were irradiated （5 days per week, 30 minutes per day, 10 000 Ix, over a 4-week period）, the exercise ＋ light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise ＋ light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise ＋ light group. These results indicate that low-intensity treadmill exercise （first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min） or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

Emerging Noninvasive Neurostimulation Technologies: CN-NINM and SYMPATOCORECTION

Two emerging noninvasive neurostimulation technologies, based on electrocutaneius stimulation of the tongue (CN-NINM) and the neck (SYMPATOCORRECTION) are presented. Currently, two portable devices were developed and introduced in clinical practice: PoNSTM (portable neurostimulator) and SYMPATOCOR. Both technologies are complement each other and demonstrate perspectives in various applications for purpose of neurorehabilitation and neurological symptoms management in such difficult rehabilitation areas, as traumatic brain injury, stroke, Parkinson’s disease, multiple sclerosis and many other neurological disorders.

Transdisciplinary Team in Rehabilitation of Unconscious Brain-Damaged Persons: Grounds and Practice

The main features of early rehabilitation after severe brain damage are discussed in the article. The most important component for the entire rehabilitation process and the subsequent life of the patient is considered restoration of consciousness. Team seems to be a key factor in regaining consciousness along with the restoration of vital functions, movement, cognition, and behavior in these patients. The basic working principle is feedback to any minimal movement, or vegetative signal of a patient, beyond specific professional targets. A network of feedbacks with a patient and between professionals, that is, free flow of information, can be built only through work in a transdisciplinary team mode. The net of feedbacks with the patient and inter-professional ones builds up the team as Non-linear Complex System. Characteristics of “Team-Patient” system status are energy, entropy, and complexity. Teamwork techniques are individualized for resulting optimization of system condition. Increase of complexity is a powerful tool for propulsion of recovery process. Then consciousness may appear as a result of system self-organization. The article reflects the authors’ view on interdisciplinary studies of the phenomenon of consciousness through its impairment and recovery. It focuses on the work of the “proper rehabilitation team”, the mechanisms of its action and methods for researching the occurring phenomena.

Overview of botulinum toxin as a treatment for spasticity in stroke patients

Spasticity after the occurrence of stroke induces limb deformity, functional disability and/or pain in patients, which limits their activities of daily living and deteriorates their quality of life. Botulinum toxin(BTX) has recently been reported as an efficacious therapeutic agent for the treatment of spasticity. Systematic review and meta-analysis studies have demonstrated that BTX therapy after stroke reduces spasticity and increases physical activity capacity and performance levels. Moreover, BTX can be used as an adjuvant in physiotherapy. Several studies have confirmed that the combination of BTX therapy and physiotherapy improves motor recovery. However, to date, only a few such combination studies have been conducted and their findings are considered preliminary and controversial. Therefore, future studies are required to determine the appropriate combination of treatment methods that will aid motor recovery.

The current state of knowledge on the clinical and methodological aspects of extracorporeal shock waves therapy in the management of post-stroke spasticity-overview of 20 years of experiences

Background and objectives In many patients after stroke, spasticity develops over time, resulting in a decrease in the patient′s independence, pain, worsening mood, and, consequently, lower quality of life. In the last ten years, a rich arsenal of physical agents to reduce muscle tone such as extracorporeal shock therapy (ESWT) wave has come through. The aim of this narrative review article is to present the current state of knowledge on the use of ESWT as a supplement to the comprehensive rehabilitation of people after stroke suffering from spasticity.Methods The PubMed and PEDro databases were searched for papers published in English from January 2000 to December 2020, 22 of which met inclusion criteria for clinical studies related to post-stroke spasticity management with ESWT.Results A total of 22 studies including 468 post-stroke patients-11 reports with the upper limb (267 patients) and 10 reports within the lower limb (201 patients), as well as one report including both upper and lower limb. We focused our attention on clinical and methodological aspects. Therefore, we performed the assessment of enrolled studies in terms of methodological quality using the PEDro and level of evidence using the National Institute for Health and Clinical Excellence (NICE) guidelines. Furthermore, we indicated implications for clinical practice in using ESWT for post-stroke spasticity management. Moreover, we discussed a suggestion for future research directions.Conclusions In conclusion, an ESWT effectively reduces muscle tone in people with spastic limb after stroke. Further, ESWT is safe and free of undesirable side effects.The mechanism of action of ESWT on muscles affected by spasticity is still unknown.To date, no standard parameters of ESWT in post-stroke spasticity regarding intensity, frequency, location, and the number of sessions has been established. Further research, meeting the highest standards, is needed to establish uniform muscle stimulation parameters using ESWT.

Autologous bone marrow mononuclear cell transplantation in patients with chronic traumatic brain injury-a clinical study

Background:Chronic Traumatic Brain Injury(TBI)is one of the common causes of longterm disability worldwide.Cell transplantation has gained attention as a prospective therapeutic option for neurotraumatic disorders like TBI.The postulated mechanism of cell transplantation which includes angiogenesis,axonal regeneration,neurogenesis and synaptic remodeling,may tackle the pathology of chronic TBI and improve overall functioning.Methods:To study the effects of cell transplantation,50 patients with chronic TBI were enrolled in an open label nonrandomized study.The intervention included intrathecal transplantation of autologous bone marrow mononuclear cells and neurorehabilitation.Mean follow up duration was 22 months.Fifteen patients underwent second dose of cell transplantation,6 months after their first intervention.Percentage analysis was performed to analyze the symptomatic improvements in the patients.Functional independence measure(FIM)was used as an outcome measure to evaluate the functional changes in the patients.Statistical tests were applied on the pre-intervention and post-intervention scores for determining the significance.Comparative Positron Emission Tomography-computed tomography(PET CT)scans were performed in 10 patients to monitor the effect of intervention on brain function.Factors such as age,multiple doses,time since injury and severity of injury were also analyzed to determine their effect on the outcome of cell transplantation.Adverse events were monitored throughout the follow up period.Results:Overall 92%patients showed improvements in symptoms such as sitting and standing balance,voluntary control,memory,oromotor skills lower limb activities,ambulation,trunk&upper limb activity,speech,posture,communication,psychological status,cognition,attention and concentration,muscle tone,coordination,activities of daily living.A statistically significant(at p≤0.05 with p-value 0)improvement was observed in the scores of FIM after intervention on the Wilcoxon signed rank test.Better outcome of the intervention was found in patients with mild TBI,age less than 18 years and time since injury less than 5 years.Ten patients who underwent a repeat PET CT scan brain showed improved brain metabolism in areas which correlated to the symptomatic changes.Two patients had an episode of seizures which was managed with medication.They both had an abnormal EEG before the intervention and 1 of them had previous history and was on antiepileptics.No other major adverse events were recorded.Conclusion:This study demonstrates the safety and efficacy of cell transplantation in chronic TBI on long term follow up.Early intervention in younger age group of patients with mild TBI showed the best outcome in this study.In combination with neurorehabilitation,cell transplantation can enhance functional recovery and improve quality of life of patients with chronic TBI.PET CT scan brain should be explored as a monitoring tool to study the efficacy of intervention.